Study of alpelisib in children and adults with PIK3CA-Related Overgrowth Spectrum (PROS)

This trial investigates alpelisib, a medication taken by mouth as film-coated tablets or granules, to determine whether it can reduce abnormal tissue growth in people with PROS. The study includes both children aged 6 to 17 and adults aged 18 and older.

Who can participate: Participants must have a confirmed diagnosis of PROS with worsening symptoms and at least one measurable tissue growth of 2 centimeters or larger. They need documented evidence of a PIK3CA gene mutation confirmed by laboratory tests. Blood sugar levels must be controlled, with fasting glucose at or below 140 mg/dL and HbA1c at or below 6.5%. Physical functioning must be adequate, with a Karnofsky score of 50 or higher for those over 16, or a Lansky score of 50 or higher for those 16 and younger.

Who cannot participate: People with a history of severe allergic reactions to alpelisib or similar medications, active cancer or cancer history in the past 3 years (except successfully treated skin cancers), severe uncontrolled diabetes, pregnancy or breastfeeding, serious heart conditions including uncontrolled high blood pressure or recent heart attack, severe mental health conditions, or severe liver problems are excluded from participation.

What the study involves: Participants will receive either alpelisib or placebo tablets daily for 16 weeks, with the possibility of continued treatment. The medication works by blocking abnormal cell growth signals in affected tissues. Regular MRI scans will measure changes in tissue size, with success defined as at least a 20% reduction in the size of affected areas. The study will continue monitoring participants through June 2030.

Investigational drug: Alpelisib (BYL719) is a PI3K inhibitor that targets the specific genetic pathway involved in tissue growth. It comes in two tablet strengths: 50 mg (light yellow) and 125 mg (dark yellow).

Study on the Effects and Safety of Alpelisib for Children and Adults with Megalencephaly-Capillary Malformation Polymicrogyria Syndrome

This study focuses on Megalencephaly-Capillary Malformation Polymicrogyria Syndrome (MCAP), a related condition characterized by an unusually large brain, skin abnormalities, and brain malformations. The trial evaluates whether alpelisib can improve adaptive behavior over 24 months.

Who can participate: Participants must be between 2 and 40 years old with a confirmed diagnosis of MCAP and a neurodevelopmental disorder ranging from specific learning difficulties to severe intellectual disability. A documented PIK3CA gene mutation is required, confirmed by DNA testing. Participants must have adequate bone marrow and organ function, including normal levels of blood cells, minerals, kidney and liver function, blood sugar, and cholesterol. They must be able to swallow the medication in tablet, suspension, or granule form.

Who cannot participate: Exclusions include any serious medical condition that might interfere with the study, current use of medications that could affect results, recent or planned surgery during the study period, pregnancy or breastfeeding, allergic reactions to similar medications, inability to follow study procedures, participation in another trial within the last 30 days, history of drug or alcohol abuse, certain mental health conditions, or lack of a reliable caregiver or support system.

What the study involves: This is a double-blind study, meaning neither participants nor researchers know who receives the actual medication or placebo. Assessments will be conducted at 6, 12, 18, and 24 months to evaluate changes in adaptive behavior, brain volume using MRI scans, and other health indicators. The study monitors quality of life, neuropsychological functions such as attention, cognition, and motor skills, as well as any side effects.

Investigational drug: Alpelisib works by inhibiting a specific enzyme involved in cell growth and survival, potentially helping reduce abnormal cell growth associated with MCAP. It is taken orally and is classified as a PI3K inhibitor.

Study of alpelisib in children and adults with PIK3CA-Related Overgrowth Spectrum (PROS)

This trial tests alpelisib in both children aged 2 and older and adults to determine how well it works in treating PROS. The study lasts up to 168 weeks with daily doses up to 250 milligrams.

Who can participate: Participants must be at least 2 years old with a confirmed PROS diagnosis showing worsening symptoms affecting multiple body areas. A confirmed PIK3CA gene mutation through DNA testing is required, with tissue samples available or obtainable through biopsy if medically safe. Physical functioning requirements include a Karnofsky score of 50 or higher for those over 16, or a Lansky score of 50 or higher for those 16 and younger. Participants must have at least mild symptom severity and at least one measurable growth of 2 centimeters or larger that causes problems or limitations in daily life.

Who cannot participate: Exclusions include age below 2 years, active cancer or cancer history in the past 3 years (except adequately treated non-melanoma skin cancer or cervical cancer), known severe allergic reactions to alpelisib, severe liver disease, uncontrolled diabetes, pregnancy or breastfeeding, use of other investigational drugs within 30 days, severe heart conditions including recent heart attack or heart failure with symptoms, severe kidney disease requiring dialysis, any medical condition that would make participation unsafe, inability to swallow oral medications, or mental conditions preventing understanding of study requirements.

What the study involves: The medication is available as film-coated tablets or granules taken orally. Regular assessments include MRI scans to measure tissue growths, pain evaluations using specific assessment tools, and blood samples to measure medication levels. Vital signs, laboratory values, cardiac function, and for applicable ages, growth, bone and dental development, and sexual maturation will be monitored. Healthcare visits and any required surgical procedures will be documented through 2030.

Investigational drug: Alpelisib (BYL719) selectively inhibits the PIK3CA enzyme responsible for cellular growth and division, targeting the genetic changes that cause abnormal tissue growth in PROS.

Study of RLY-2608 for Adults and Children with PIK3CA-Related Overgrowth and Malformations

This study investigates RLY-2608, a new treatment taken as a capsule, designed to target and inhibit the specific protein affected by PIK3CA mutations. The trial aims to find the best dose and assess safety and effectiveness.

Who can participate: Participants aged 2 to 17 years must have a clinical diagnosis of PROS or a malformation classified by ISSVA 2018. They need documented activating PIK3CA mutations in affected tissue or cell-free DNA from the lesion or blood. Participants must agree to provide archived fluid or tissue samples, or undergo a biopsy if medically safe. They must have a Lansky performance status of 50 or higher if under 16, or Karnofsky performance status of 50 or higher if 16 or older.

Who cannot participate: Exclusions include any serious health condition that might interfere with the study, pregnancy or breastfeeding, participation in another clinical trial within 30 days, known allergies to the study medication or ingredients, inability to follow study procedures, history of certain cancers unless in remission for a specified period, severe liver or kidney disease, uncontrolled high blood pressure, history of heart attack or stroke within the last 6 months, or current use of medications that might interfere with the study drug.

What the study involves: The study has multiple parts, initially finding the most suitable dose while monitoring side effects. Later, RLY-2608's effectiveness will be compared to placebo to see how well it reduces overgrowth or malformations. Participants will be monitored over time for changes in lesion volume, with regular check-ups to assess response to treatment and track any side effects.

Investigational drug: RLY-2608 is a PI3Kα inhibitor that selectively targets the mutant form of the PI3Kα enzyme, which plays a role in cell growth and survival. It potentially reduces abnormal cell proliferation in affected areas.

Long-term Safety Study of Miransertib for Patients with PIK3CA-related Overgrowth Spectrum or Proteus Syndrome

This trial evaluates the long-term safety of miransertib, an oral medication in hard capsule form, for people with PROS or Proteus Syndrome. Participants are those already receiving miransertib in other studies.

Who can participate: Participants aged 2 to 120 years must have PROS or Proteus Syndrome and have been previously treated with miransertib in specific studies or be approved by the sponsor to screen. Male participants must agree to use contraception or abstain from heterosexual intercourse during the study and for 90 days after the last dose, unless confirmed unable to produce sperm. Female participants must not be pregnant or breastfeeding and agree to use highly effective contraception or abstain from sexual intercourse if they can have children.

Who cannot participate: Exclusions include any serious medical condition that might interfere with the study, pregnancy or breastfeeding, participation in another clinical trial within 30 days, known allergies to the study medication or ingredients, inability to comply with study procedures, history of drug or alcohol abuse within the past year, certain heart conditions that could be affected by the medication, use of medications that might interact with the study drug, history of certain cancers, or uncontrolled diabetes or high blood pressure.

What the study involves: The study monitors participants to see if they experience any serious side effects or need to stop taking the medication due to adverse effects. Regular follow-up visits are scheduled to ensure safety and effectiveness, with the study expected to conclude by December 2025.

Investigational drug: Miransertib is a selective allosteric AKT inhibitor that targets specific pathways in the body involved in cell growth and survival. It works by controlling the symptoms associated with PROS and Proteus Syndrome by targeting molecular mechanisms contributing to abnormal tissue growth.

Study on the Long-Term Safety of Alpelisib for Patients with PIK3CA-Related Overgrowth Spectrum (PROS)

This study evaluates the long-term safety and tolerability of alpelisib in patients who have previously participated in a related study called EPIK-P1. The medication is taken as a film-coated tablet.

Who can participate: Participants of various ages including children, teenagers, and adults must have previously participated in the EPIK-P1 study. They or their parent/guardian must sign an informed consent form. Participants must have taken at least one dose of alpelisib after March 9, 2020. Those who stopped taking the medication for safety reasons before the new study period can still participate by providing past data. Those who stopped for other reasons, such as worsening condition, can restart treatment if the study doctor believes it will help.

Who cannot participate: Exclusions include having a medical condition other than PROS that could interfere with the study, not being within the specified age range, inability to follow study procedures, pregnancy or breastfeeding, recent participation in another clinical trial, history of allergic reactions to the study medication, serious medical conditions that could affect safety, use of medications that could interfere with the study drug, history of drug or alcohol abuse, or mental health conditions that could affect ability to participate.

What the study involves: Participants will take alpelisib orally as determined by the study team based on individual needs and previous treatment history. The study monitors patients over time to check for any new or worsening side effects. Regular assessments include laboratory tests, vital signs, and cardiac function evaluations. Additional evaluations may include growth, bone and dental development, and sexual maturation for applicable ages. The study will gather information on healthcare visits or hospitalizations due to PROS and any other treatments or surgeries related to the condition. The study is expected to continue until September 2027.

Investigational drug: Alpelisib is a PI3K inhibitor that works by blocking the PI3K enzyme, which plays a role in cell growth and division, thereby helping to control abnormal cell proliferation in tissues affected by PIK3CA gene mutations.

PIK3CA related overgrowth spectrum Trials in Disease

Clinical trial locations

Study on the Effects and Safety of Alpelisib for Children and Adults with Megalencephaly-Capillary Malformation Polymicrogyria Syndrome

Summary

Clinical trials for PIK3CA related overgrowth spectrum